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| Open AccessElongator and codon bias regulate protein levels in mammalian peripheral neurons
Familial dysautonomia is linked to mutations in IKBKAP, a scaffolding protein for the Elongator complex, which regulates codon-biased gene translation in yeast. Here the authors show in mammalian neurons that IKBKAP loss alters expression of codon-biased genes, including some involved in DNA damage.
- Joy Goffena
- , Frances Lefcort
- & Lynn George
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Article
| Open AccessThe effects of death and post-mortem cold ischemia on human tissue transcriptomes
RNA levels in post-mortem tissue can differ greatly from those before death. Studying the effect of post-mortem interval on the transcriptome in 36 human tissues, Ferreira et al. find that the response to death is largely tissue-specific and develop a model to predict time since death based on RNA data.
- Pedro G. Ferreira
- , Manuel Muñoz-Aguirre
- & Roderic Guigó
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Article
| Open AccessA general and flexible method for signal extraction from single-cell RNA-seq data
Single-cell RNA sequencing (scRNA-seq) data provides information on transcriptomic heterogeneity within cell populations. Here, Risso et al develop ZINB-WaVE for low-dimensional representations of scRNA-seq data that account for zero inflation, over-dispersion, and the count nature of the data.
- Davide Risso
- , Fanny Perraudeau
- & Jean-Philippe Vert
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Article
| Open AccessMicrobiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases
Histone post-translational modifications are known key regulators of gene expression. Here, the authors characterize histone crotonylation at histone H3 lysine 18 in intestinal epithelia and find that it is a highly dynamic cell cycle regulated mark under the regulation of the HDAC deacetylases.
- Rachel Fellows
- , Jérémy Denizot
- & Patrick Varga-Weisz
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Article
| Open AccessTranscriptional signatures of schizophrenia in hiPSC-derived NPCs and neurons are concordant with post-mortem adult brains
Induced pluripotent stem cell (hiPSC)-based models have inherent variations in their cellular and molecular output and readouts. Here, Hoffman and colleagues devise a method to account for gene expression variations in hiPSC-derived neurons from patients with childhood-onset schizophrenia.
- Gabriel E. Hoffman
- , Brigham J. Hartley
- & Kristen J. Brennand
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Article
| Open AccessMating system manipulation and the evolution of sex-biased gene expression in Drosophila
Sexual selection on males is thought to favour male-biased gene expression. Here, Veltsos et al. experimentally evolve Drosophila pseudoobscura under different mating systems and, contrary to expectation, most often find masculinization of the transcriptome under monogamy rather than under elevated polyandry.
- Paris Veltsos
- , Yongxiang Fang
- & Michael G. Ritchie
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Article
| Open AccessA multiplexable TALE-based binary expression system for in vivo cellular interaction studies
Binary expression systems enable researchers to deliver loss-of-function or gain-of-function transgenes with spatial-temporal resolution in vivo. Here, the authors present a programmable TALE-based system for multiplexed orthogonal activation of transgenes in Drosophila.
- Markus Toegel
- , Ghows Azzam
- & Tudor A. Fulga
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Article
| Open AccessRapid neo-sex chromosome evolution and incipient speciation in a major forest pest
The evolution of new sex chromosomes potentially generates reproductive isolation. Here, Bracewell et al. combine crossing experiments with population and functional genomics to characterize neo-sex chromosome evolution and incipient speciation in the mountain pine beetle, Dendroctonus ponderosae.
- Ryan R. Bracewell
- , Barbara J. Bentz
- & Jeffrey M. Good
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Article
| Open AccessGenome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus
Most SNPs are located in non-coding genomic regions and their function remains elusive. Here, the authors perform a genome-wide scan of expression and DNA methylation quantitative trait loci in human hippocampal tissue to provide a resource for the functional interpretation of SNPs in brain disorders.
- Herbert Schulz
- , Ann-Kathrin Ruppert
- & Sven Cichon
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Article
| Open AccessMapping genomic and transcriptomic alterations spatially in epithelial cells adjacent to human breast carcinoma
Studying the spatial mutational and gene expression alterations in breast cancer could impact our understanding of breast cancer development. Here, the authors analyse a unique dataset of epithelial samples that highlight potential field cancerisation surrounding the primary tumour.
- Moustafa Abdalla
- , Danh Tran-Thanh
- & Susan J. Done
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Article
| Open AccessSystematic proteome and proteostasis profiling in human Trisomy 21 fibroblast cells
Trisomy 21 (T21) is a major cause of Down syndrome but little is known about its impact on the cellular proteome. Here, the authors define the proteome of T21 fibroblasts and its turnover and also map proteomic differences in monozygotic T21-discordant twins, revealing extensive, organelle-specific changes caused by T21.
- Yansheng Liu
- , Christelle Borel
- & Ruedi Aebersold
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Article
| Open AccessDNA-binding of the Tet-transactivator curtails antigen-induced lymphocyte activation in mice
Tet-transactivators are used for direct regulation of gene expression, RNA interference and for CRISPR/Cas9-based systems. Here the authors show that DNA-bound Tet-transactivators can induce cell death in antigen-activated lymphocytes in vivo, putting into question the use of, and in vivo data generated with, these molecular tools.
- Eleonora Ottina
- , Victor Peperzak
- & Andreas Villunger
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Article
| Open AccessEstablishing multiple omics baselines for three Southeast Asian populations in the Singapore Integrative Omics Study
The Singapore Genome Variation projects characterized the genetics of Singapore’s Chinese, Malay, and Indian populations. The Singapore Integrative Omics Study introduced here goes further in providing multi-omic measurements in individuals from these populations, including genetic, transcriptome, lipidome, and lifestyle data, and will facilitate the study of common diseases in Asian communities.
- Woei-Yuh Saw
- , Erwin Tantoso
- & Yik-Ying Teo
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Article
| Open AccessGenetic correlations reveal the shared genetic architecture of transcription in human peripheral blood
Covariance of gene expression pairs is due to a combination of shared genetic and environmental factors. Here the authors estimate the genetic correlation between highly heritable pairs and identify transcription factor control and chromatin interactions as possible mechanisms of correlation.
- Samuel W. Lukowski
- , Luke R. Lloyd-Jones
- & Joseph E. Powell
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Article
| Open AccessThe Gcn4 transcription factor reduces protein synthesis capacity and extends yeast lifespan
The transcription factor Gcn4 is known to regulate yeast amino acid synthesis. Here, the authors show that Gcn4 also acts as a repressor of protein biosynthesis in a range of conditions that enhance yeast lifespan, such as ribosomal protein knockout, calorie restriction or mTOR inhibition.
- Nitish Mittal
- , Joao C. Guimaraes
- & Mihaela Zavolan
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Article
| Open AccessSingle cardiomyocyte nuclear transcriptomes reveal a lincRNA-regulated de-differentiation and cell cycle stress-response in vivo
Adult mammalian cardiomyocytes are predominantly binucleated and unable to divide. Using single nuclear RNA-sequencing of cardiomyocytes from mouse and human failing and non-failing adult hearts, See et al. show that some cardiomyocytes respond to stress by dedifferentiation and cell cycle re-entry regulated by lncRNAs.
- Kelvin See
- , Wilson L. W. Tan
- & Roger S. Foo
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| Open AccessBivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus
Bone mineral density and lean skeletal mass are heritable traits. Here, Medina-Gomez and colleagues perform bivariate GWAS analyses of total body lean mass and bone mass density in children, and show genetic loci with pleiotropic effects on both traits.
- Carolina Medina-Gomez
- , John P. Kemp
- & Fernando Rivadeneira
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Article
| Open AccessLarge meta-analysis of genome-wide association studies identifies five loci for lean body mass
Lean body mass is a highly heritable trait and is associated with various health conditions. Here, Kiel and colleagues perform a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.
- M. Carola Zillikens
- , Serkalem Demissie
- & Douglas P. Kiel
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Article
| Open AccessFacultative CTCF sites moderate mammary super-enhancer activity and regulate juxtaposed gene in non-mammary cells
Chromatin neighbourhoods, formed by CTCF, have been proposed to isolate enhancers and their target genes from other regulatory elements. Here, the authors provide evidence that while CTCF binding does regulates mammary-specific super-enhancers, CTCF sites are relatively porous borders.
- M. Willi
- , K. H. Yoo
- & L. Hennighausen
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Article
| Open AccessFlipping between Polycomb repressed and active transcriptional states introduces noise in gene expression
Polycomb repressive complexes modify histones but it is unclear how changes in chromatin states alter kinetics of transcription. Here, the authors use single-cell RNAseq and ChIPseq to find that actively transcribed genes with Polycomb marks have greater cell-to-cell variation in expression.
- Gozde Kar
- , Jong Kyoung Kim
- & Sarah A. Teichmann
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Article
| Open AccessA damaged genome’s transcriptional landscape through multilayered expression profiling around in situ-mapped DNA double-strand breaks
DNA double strand breaks (DSBs) are among the most deleterious types of damage and there is strong evidence indicating a relationship between breaks and transcription. Here the authors provide a high-resolution, genome-wide map of induced DSBs and observe ATM-dependent transcriptional repression.
- Fabio Iannelli
- , Alessandro Galbiati
- & Fabrizio d’Adda di Fagagna
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Article
| Open AccessSelective analysis of cancer-cell intrinsic transcriptional traits defines novel clinically relevant subtypes of colorectal cancer
Stromal cells contribute to the gene expression profiles based on which colorectal cancer (CRC) molecular subtypes are classified. Here, patient-derived xenografts enable the authors to obtain cancer cell-specific transcriptomes by excluding transcripts from murine stromal cells, based on which they define CRC intrinsic subtypes (CRIS) and evaluate their prognostic and predictive potential.
- Claudio Isella
- , Francesco Brundu
- & Andrea Bertotti
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Article
| Open AccessA complete tool set for molecular QTL discovery and analysis
Analysis of molecular quantitative trait loci (molQTL) can help interpret genome-wide association studies and requires efficient approaches to correct for multiple testing. This study describes a bioinformatics toolkit called QTLtool that can handle large data sets and quickly perform multiple types of molQTL analyses.
- Olivier Delaneau
- , Halit Ongen
- & Emmanouil T. Dermitzakis
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Article
| Open AccessLamin B1 is required for mature neuron-specific gene expression during olfactory sensory neuron differentiation
Emerging evidence suggests that lamins regulate gene expression during cellular differentiation. Giganteet al. show that lamin B1 is necessary for the upregulation of mature neuron-specific genes during olfactory neuron differentiation, and its deficiency leads to attenuated olfactory neuron response to odour in mice.
- Crystal M. Gigante
- , Michele Dibattista
- & Haiqing Zhao
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Article
| Open AccessRotiferan Hox genes give new insights into the evolution of metazoan bodyplans
Rotifers are microscopic animals with an unusual, nonsegmented body plan consisting of a head, trunk and foot. Here, Fröbius and Funch investigate the role of Hox genes—which are widely used in animal body plan patterning—in rotifer embryogenesis and find non-canonical expression in the nervous system.
- Andreas C. Fröbius
- & Peter Funch
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Correspondence
| Open AccessCorrespondence: Reply to ‘Oncogenic MYC persistently upregulates the molecular clock component REV-ERBα’
- Anton Shostak
- , Bianca Ruppert
- & Michael Brunner
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Correspondence
| Open AccessCorrespondence: Oncogenic MYC persistently upregulates the molecular clock component REV-ERBα
- Brian J. Altman
- , Annie L. Hsieh
- & Chi V. Dang
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Article
| Open AccessDynamic transcriptomes identify biogenic amines and insect-like hormonal regulation for mediating reproduction in Schistosoma japonicum
For reproduction, the human parasiteSchistosoma japonicumrelies on a complex and incompletely understood interplay between female and male schistosomes. Here the authors sequence the transcriptome of female and male schistosomes across eight time points during sexual development.
- Jipeng Wang
- , Ying Yu
- & Wei Hu
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Article
| Open AccessIntegrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease
Epigenetic perturbations may be an important factor in diseases where both genes and environment play a role. Here, Ventham and colleagues show that DNA methylation changes in inflammatory bowel disease are related to the underlying genotype, and are associated with cell-specific changes to gene expression.
- N. T. Ventham
- , N. A. Kennedy
- & J. Satsangi
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Article
| Open AccesstRNA-mediated codon-biased translation in mycobacterial hypoxic persistence
Mycobacteria can adapt to the stress of human infection by entering a dormant state. Here the authors show that hypoxia-induced dormancy in M. bovisBCG involves the reprogramming of tRNA wobble modifications and copy numbers, coupled with biased use of synonymous codons in survival genes.
- Yok Hian Chionh
- , Megan McBee
- & Peter C. Dedon
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Article
| Open AccessMassive and parallel expression profiling using microarrayed single-cell sequencing
Currently available single-cell transcriptomic analyses are expensive and low throughput. Here, Vickovicet al. describe a new method called MASC-seq that is based on microarray barcoding of expression pattern and of low cost with high robustness.
- Sanja Vickovic
- , Patrik L. Ståhl
- & Joakim Lundeberg
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Article
| Open AccessLoss of RNA expression and allele-specific expression associated with congenital heart disease
Congenital heart disease (CHD) is a disorder that occurs in ∼1% of live births. Here the authors describe a genome-wide allele-specific expression analyses in CHD patients, identifying five new genes involved in CHD and showing that paternally-expressed imprinted genes are monoallelic, while maternally-expressed imprinted genes are biallelic.
- David M. McKean
- , Jason Homsy
- & J. G. Seidman
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Article
| Open AccessTwister ribozymes as highly versatile expression platforms for artificial riboswitches
Twister ribozymes are small endonucleolytic RNA motifs. Here the authors develop twister ribozymes into RNA logic gates and cross-species synthetic genetic regulators.
- Michele Felletti
- , Julia Stifel
- & Jörg S. Hartig
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Article
| Open AccessExtraction and analysis of signatures from the Gene Expression Omnibus by the crowd
A wealth of gene expression data is publicly available, yet is little use without additional human curation. Ma’ayan and colleagues report a crowdsourcing project involving over 70 participants to annotate and analyse thousands of human disease-related gene expression datasets.
- Zichen Wang
- , Caroline D. Monteiro
- & Avi Ma’ayan
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Article
| Open AccessWriting of H3K4Me3 overcomes epigenetic silencing in a sustained but context-dependent manner
Epigenome editing by zinc finger (ZF) and CRISPR-dCas9 technologies can induce or repress gene expression. Here, the authors show that histone methyltransferase PRDM9 fused to either dCas9 or ZF proteins can sustain gene re-expression, and H3K79me is required for stable gene re-expression.
- David Cano-Rodriguez
- , Rutger A F. Gjaltema
- & Marianne G Rots
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Article
| Open AccessWidespread adaptive evolution during repeated evolutionary radiations in New World lupins
Species radiations can be driven by both adaptive and non-adaptive processes, but the relative importance of these drivers is unknown. Here, Nevado et al. show that multiple radiations in the New World lupins were associated with genome-wide accelerations in both coding and regulatory evolution, suggesting a strong influence of adaptive processes.
- Bruno Nevado
- , Guy W. Atchison
- & Dmitry A. Filatov
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Article
| Open AccessAscarosides coordinate the dispersal of a plant-parasitic nematode with the metamorphosis of its vector beetle
Many species of nematodes use pheromones called ascarosides to coordinate their behaviour and development. Here, Zhao et al. demonstrate that the beetle vector of the pinewood nematode (Bursaphelenchus xylophilus) also uses and responds to ascarosides in its interactions with the nematodes.
- Lilin Zhao
- , Xinxing Zhang
- & Jianghua Sun
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Article
| Open AccessMolecular signatures of neural connectivity in the olfactory cortex
The piriform cortex projects to multiple brain regions involved in diverse aspects of olfactory behavior but information about the organization of these outputs is lacking. Here the authors show that piriform neurons exhibit layer specific gene expression patterns that also define distinct projection targets.
- Assunta Diodato
- , Marion Ruinart de Brimont
- & Alexander Fleischmann
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Article
| Open AccessThe multicellularity genes of dictyostelid social amoebas
Unicellular social amoebae aggregate to form a multicellular life stage, making them a model system for the evolution of multicellularity. Here, Glöckner et al.use a comparative genomic and transcriptomic approach to determine the origin of the genes essential for multicellularity in the social amoebae.
- Gernot Glöckner
- , Hajara M. Lawal
- & Pauline Schaap
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Article
| Open AccessMYC/MIZ1-dependent gene repression inversely coordinates the circadian clock with cell cycle and proliferation
The circadian clock and the cell cycle systems coordinate global physiology. Here the authors show that MYC represses the clock genes, together with MIZ1, and induces proliferation, suggesting that MYC inversely modulates cell cycle and circadian clock genes.
- Anton Shostak
- , Bianca Ruppert
- & Michael Brunner
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Article
| Open AccessHsf1 and Hsp90 orchestrate temperature-dependent global transcriptional remodelling and chromatin architecture in Candida albicans
The transcription factor Hsf1 and the molecular chaperone Hsp90 modulate the heat shock response in the pathogen Candida albicans. Here, Leach et al. reveal a complex interplay between the two factors that regulates the expression of genes involved in the heat shock response and virulence.
- Michelle D. Leach
- , Rhys A. Farrer
- & Leah E. Cowen
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Article
| Open AccessNeutrophil-specific deletion of the CARD9 gene expression regulator suppresses autoantibody-induced inflammation in vivo
Neutrophils play an important role in antimicrobial host defence but can also contribute to non-infectious inflammatory processes. Here the authors show that adaptor protein CARD9 expressed in neutrophils is involved in the development of sterile auto-antibody-mediated inflammatory reactions.
- Tamás Németh
- , Krisztina Futosi
- & Attila Mócsai
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Article
| Open AccessQuaking promotes monocyte differentiation into pro-atherogenic macrophages by controlling pre-mRNA splicing and gene expression
Post-transcriptional control of RNA is important in health and disease. Here, the authors show that the RNA-binding protein Quaking guides pre-mRNA splicing and transcript abundance during monocyte to macrophage differentiation, and that Quaking depletion impairs pro-atherogenic foam cell formation.
- Ruben G. de Bruin
- , Lily Shiue
- & Eric P. van der Veer
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Article
| Open AccessLoss of MAX results in meiotic entry in mouse embryonic and germline stem cells
The mechanisms that trigger meiosis in germ cells and halt this process in non-germline cells are unclear. Here, the authors show that knockout of Maxin embryonic stem cells results in meiotic onset in a mechanism that involves the PRC1 complex.
- Ayumu Suzuki
- , Masataka Hirasaki
- & Akihiko Okuda
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Article
| Open AccessRegulation of cell-to-cell variability in divergent gene expression
Gene expression noise affects cell fitness and development. Here, Yan et al. show that co-regulated divergent gene pairs (DGPs) suppress uncorrelated gene expression noise due to more synchronized transcription firing, and differentially regulated DGPs enhance gene expression noise due to transcription leakage.
- Chao Yan
- , Shuyang Wu
- & Lu Bai
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Article
| Open AccessSingle-cell differences in matrix gene expression do not predict matrix deposition
Regenerative tissue engineering with mesenchymal stem cells is hampered by bulk methods of assessing differentiation status and a general assumption that expression of individual markers of stem cell differentiation correlate with functional capacity. Here the authors debunk this assumption by applying single-cell techniques to disassociate aggrecan mRNA abundance and matrix deposition.
- Allison J. Cote
- , Claire M. McLeod
- & Robert L. Mauck
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Article
| Open AccessSynthetic RNA–protein modules integrated with native translation mechanisms to control gene expression in malaria parasites
Current strategies for regulatory control of gene expression are orthogonal to the host organism mechanisms. Here the authors demonstrate an RNA aptamer controlled system integrated into native regulatory pathways in the parasite Plasmodium falciparum.
- Suresh M. Ganesan
- , Alejandra Falla
- & Jacquin C. Niles
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Article
| Open AccessStem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer
Gene-expression profiles can be used to predict the prognosis of cancer patients. Here, the authors describe gene expression profiles of human prostate epithelial lineages and show that basal cells have intrinsic stem and neurogenic properties, and molecularly resemble aggressive prostate cancer.
- Dingxiao Zhang
- , Daechan Park
- & Dean G. Tang
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Article
| Open AccessHuman oocyte developmental potential is predicted by mechanical properties within hours after fertilization
Reliable assessments of oocyte developmental potential are lacking, making it difficult to select the best quality embryos for transfer after in vitrofertilization. Here, the authors show that a non-invasive measurement of viscoelastic properties predicts developmental potential in both humans and mice.
- Livia Z. Yanez
- , Jinnuo Han
- & David B. Camarillo